This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.
Amino Acid Sequence ; Cloning, Molecular ; Geranyltranstransferase/genetics* ; Pogostemon ; Transcription Factors/genetics*

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guideline 2019 recommended that lymph node dissection for advanced rectal cancer should include the lymphatic adipose tissue at the root of the inferior mesenteric vessels, but the ligation site of the inferior mesenteric artery (IMA) was not determined, and the NCCN guideline did not indicate clearly whether to retain the left colonic artery (LCA). Controversy over whether to retain LCA is no more than whether it can reduce the incidence of anastomotic complications or postoperative functional damage without affecting the patients' oncological outcome. Focusing on the above problems, this paper reviews the latest research progress. In conclusion, it is believed that the advantages of retaining LCA are supported by most studies, which can improve the blood supply of the proximal anastomosis, and technically can achieve the same range of lymph node dissection as IMA high ligation. However, whether it affects the survival of patients, reduces the incidence of anastomotic leakage, and improves the quality of life of patients, more high-quality evidence-based medical evidence is still needed.
Arteries ; Humans ; Laparoscopy ; Mesenteric Artery, Inferior/surgery* ; Quality of Life ; Rectal Neoplasms/surgery*

Acquired Immunodeficiency Syndrome/drug therapy* ; Antiretroviral Therapy, Highly Active ; HIV Infections/drug therapy* ; Humans

Objectives:To analyze the clinical characteristics, etiological distribution of inpatients with syncope in our center. Methods:Patients with syncope were consecutively enrolled from September 2014 to April 2017 in Center of Arrhythmia of Fuwai Hospital. Demographics, medical history, physical examination results and laboratory tests were collected according to screen algorism to investigate the possible etiologies of syncope. Risk stratification was performed based on guidelines for the diagnosis and management of syncope (version 2009,ESC)and Chinese expert consensus on the diagnosis and treatment of syncope (version 2014). Results:After collecting medical history, physical examination and performing laboratory tests, three hundred patients who experienced the latest syncope within 180 days before admission was identified from 5 191 patients, the average age was (57.7 ± 15.4) years, 177 (59.0%) were male, 235 (78.3%) experienced syncope within 30 days before admission, 9.7% patients had recurrent episodes, 80.7% were defined as high risk syncope patients, 144(48.0%)patients suffered structural heart disease. Cardiac syncope was the most common etiology (214 cases,71.3%), followed by reflex syncope(44 cases,14.7%) and orthostatic hypotension (8 cases,2.7%), while etiology was not identified in the rest 34 patients (11.3%). Among all the etiologies of syncope, brandy arrhythmia was the most common reason for syncope (37.3% [112 cases]). During onset of syncope prior to hospitalization, five patients were diagnosed with severe intracranial hematoma or cerebral hemorrhage, six cardiopulmonary resuscitations were performed, and eleven patients received external direct current cardioversion. Conclusions:Etiology could be defined in most of the syncope patients admitted to our center, the prevalence of high-risk syncope and syncope due to brady arrhythmias is high in this patient cohort, treatments of the syncope patients could be improved by etiological and timely prognosis.

Objective: To explore the safety and efficacy of a novel lead locking device (LLD) in the procedure of cardiac lead extraction for heart rhythm implants. Methods: A total of 6 patients using LLD for cardiac lead extraction in our hospital were retrospectively reviewed. Clinical parameters, the reason of cardiac lead extraction, lead locking stylet condition, outcome of lead extraction and operative complications were summarized. Results: There were 6 patients including 1 female with the median age at 62.5 years. LLD was used and 13 cardiac leads were extracted including 1 scrap electrode wire and 12 functional electrode wire. Among those, LLD was successfully inserted and locked on the top of 11/13 (85%) leads for whole procedure and 2 (15%) leads were not locked for whole procedure; 12 (92 %) leads were completely removed and 1 (8%) lead was partially removed. No severe complications occurred. Conclusion: The novel LLD may safely and effectively extract electrode lead which is beneficial for complete cardiac lead extraction.

BACKGROUNDAcute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.

METHODSA randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).

RESULTSEtoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).

CONCLUSIONSEtoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).

Adult ; Aged ; Arthritis, Gouty ; drug therapy ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Indomethacin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyridines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use

OBJECTIVETo explore the clinical therapeutic effect of acupuncture on Alzheimer's disease (AD) and its mechanism.

METHODSTwenty patients with Alzheimer's disease were treated by acupuncture with reinforcing kidney and activating blood method for 12 weeks and Baihui (GV 20), Shenshu (BL 23), Xuehai (SP 10) and Geshu (BL 17) were selected. The clinical therapeutic effect were assessed by comparing the scores of Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-Cog) and 8-IPF2alpha concentration in cerebrospinal fluid, blood and urine before and after treatment were detected by using enzyme linked immunosorbent assay.

RESULTSAfter treatment, the effective rate was 90.0%. The score of ADAS-Cog was 35. 70 +/- 14. 70 before treatment and 31. 45 +/- 4. 08 after treatment, with a significant difference (P<0. 001). The concentration of 8-IPF2alpha in cerebrospinal fluid, blood and urine were all significantly decreased after treatment (all P<0.001).

CONCLUSIONAcupuncture can improve the cognitive ability of AD patients and its possible mechanism may be relative to the decrease in lipid peroxidation in AD patients' brain.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Aged, 80 and over ; Alzheimer Disease ; blood ; cerebrospinal fluid ; therapy ; urine ; Cognition ; F2-Isoprostanes ; analysis ; blood ; cerebrospinal fluid ; urine ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome